Expression and prognostic relevance of vascular endothelial growth factor (VEGF) and its receptor (FLT-1) in nephroblastoma

Ghanem, Mazen A.; Steenbrugge, G.J. van; Sudaryo, Mondastri Korib; Mathoera, Rejiv B.; Nijman, J. M.; Kwast, Theodorus H. van der

doi:10.1136/jcp.56.2.107

Cited by 68 publications

(43 citation statements)

References 38 publications

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“…A normal renal tissue section was used as a positive tissue control for flt-1, since flt-1 is expressed in the tubular structure of normal renal tissue. 8) Ki-67 staining index was calculated to evaluate the …”

Section: Methodsmentioning

confidence: 99%

Growth Potential of Orbital Cavernous Hemangioma Suggested by Vascular Endothelial Growth Factor and its Receptor Flk-1

Nagasaka

Naganuma

Satoh

2007

Neurol. Med. Chir.(Tokyo)

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Orbital cavernous hemangiomas (CHs) manifest as slowly developing symptoms indicative of slow growth. The present study investigated the involvement of angiogenic factors and their receptors in the growth of orbital CHs. Surgical specimens of orbital CHs were obtained from nine patients. Formalinfixed, paraffin-embedded specimens were stained immunohistochemically using antibodies against Ki-67, CD31, a-smooth muscle actin (a-SMA), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and VEGF receptors (flt-1 and flk-1). CD31 was expressed in the single layer of endothelial cells lining the vascular cavity. The thick vascular walls were positive for a-SMA, indicating that the vascular walls were smooth muscle cells. Ki-67 antigen immunostaining was mostly positive in the vascular walls and the staining index ranged from 0% to 6.8% (mean ± standard deviation, 2.7 ± 1.9%). VEGF and bFGF immunostaining were positive in all specimens. Flt-1 immunostaining was negative in all specimens, but flk-1 immunostaining was positive in both endothelial cells and smooth muscle cells. These results suggest that both VEGF and its receptor flk-1 are important in the growth of orbital CH.

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Section: Methodsmentioning

confidence: 99%

Growth Potential of Orbital Cavernous Hemangioma Suggested by Vascular Endothelial Growth Factor and its Receptor Flk-1

Nagasaka

Naganuma

Satoh

2007

Neurol. Med. Chir.(Tokyo)

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“…It was observed that its immunohistochemical expression in the cytoplasm of blastema neoplastic cells was correlated with risk group, clinical course and anaplasia, being higher in the high risk group among patients with relapse or fatal outcome and tumors with anaplasia. The role of VEGFR1 in the progression of Wilms' tumors had already been described by Ghanem et al (14) , who correlated VEGFR1 immunoexpression with clinical progression and fatal outcome. These findings suggest the participation of these cells in tumoral neovascularization.…”

Section: Discussionmentioning

confidence: 96%

“…Additionally, BAX immunoexpression in stroma was higher in cases with preoperative chemotherapy and mean immunoexpression of BAX was higher in tumors weighing less than 550 g. It is acknowledged that chemotherapeutic agents sensitize neoplastic cells for a higher apoptotic activity, hence its higher expression in cases with preoperative chemotherapy (15,21,33) . The angiogenesis is fundamental for tumor growth and it is under regulatory effects of a wide variety of angiogenic factors, namely vascular endothelial growth factor (VEGF) and its receptors (14) . VEGF action on endothelial cell receptors promotes angiogenesis as well as it induces the expression of antiapoptotic proteins.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical expression of p53, BCL-2, BAX and VEGFR1 proteins in nephroblastomas

Percicote¹,

Leme²,

Almeida³

et al. 2013

J. Bras. Patol. Med. Lab.

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Introduction: Nephroblastoma or Wilms' tumor is the most frequent renal cancer in children. Although its prognosis is favorable for most patients, it may relapse or have a fatal outcome. The characterization of risk groups by applying immunohistochemical biomarkers aims to adapt the treatment to its corresponding group as well as to reduce relapses and fatal outcome. p53, B-cell lymphoma 2 (BCL-2), BCL-2 associated protein X (BAX) and vascular endothelial growth factor receptor 1 (VEGFR1) are among the most widely studied biomarkers, which are related to the apoptotic pathway, DNA repair and neovascularization. Objective: The objective of this study is to assess the immunohistochemical expression of p53, BCL-2, BAX and VEGFR1 in samples of human nephroblastoma and to correlate them with clinicopathological prognostic factors. Material and methods: Twenty-nine surgical specimens of nephroblastoma diagnosed from 1994 to 2007 were selected from the Anatomopathological Service of two hospitals in Curitiba. The immunohistochemical analysis of tissue microarrays was performed through immunoperoxidase staining and the yielded results were compared with clinicopathological prognostic factors. Results: The major immunohistochemical expression of VEGFR1 in blastema and epithelium presented positive association with the risk group. Hence this may be related to higher vascular neoplastic invasion apparently caused by the endothelial growth factor, which maximizes the chances of metastasis and ultimately changes tumor staging, risk group and clinical evolution. Conclusions: The immunohistochemical expression of VEGFR1 substantiated a directly proportional association with the nephroblastoma risk group.

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“…Prior to primary tumor resection, children with cancer have increased circulating VEGF levels [11][12][13]. Primary tumor tissue from neuroblastoma [14 -17] and Wilms' tumor [18,19] expresses VEGF, with higher expression correlating with invasion, metastasis, and the risk for recurrence. VEGF overexpression can be demonstrated in primary tumors from patients with Ewing's sarcoma, although the prognostic implication is disputed [20,21].…”

Section: Vegf In Pediatric Solid Tumorsmentioning

confidence: 99%

Clinical Development of VEGF Signaling Pathway Inhibitors in Childhood Solid Tumors

2011

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After completing this course, the reader will be able to:1. Identify the mechanism, specificity, relative potency, dosing schedule, important pharmacokinetic characteristics, and agent-specific side effects of the VEGF signaling pathway inhibitors currently in pediatric development.2. Describe the different concerns between children and adults regarding the common class side effects of the VEGF pathway inhibitors.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME ABSTRACTAngiogenesis is a target shared by both adult epithelial cancers and the mesenchymal or embryonal tumors of childhood. Development of antiangiogenic agents for the pediatric population has been complicated by largely theoretical concern for toxicities specific to the growing child and prioritization among the many antiangiogenic agents being developed for adults. This review summarizes the mechanism of action and preclinical data relevant to childhood cancers and early-phase clinical trials in childhood solid tumors. Single-agent adverse event profiles in adults and children are reviewed with emphasis on cardiovascular, bone health, and endocrine side effects. In addition, pharmacological factors that may be relevant for prioritizing clinical trials of these agents in children are reviewed.Considerations for further clinical evaluation should include preclinical data, relative potency, efficacy in adults, and the current U.S. Food and Drug Administration approval status. Toxicity profiles of vascular endothelial growth factor (VEGF) signaling pathway inhibitors may be age dependent and ultimately, their utility in the treatment of childhood cancer will require combination with standard cytotoxic drugs or other molecularly targeted agents. In combination studies, toxicity profiles, potential drug interactions, and late effects must be considered. Studies to assess the long-term impact of VEGF signaling pathway inhibitors on cardiovascular, endocrine, and bone health in children with cancer are imperative if these agents are to be administered to growing children and adolescents with newly diagnosed cancers.

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Expression and prognostic relevance of vascular endothelial growth factor (VEGF) and its receptor (FLT-1) in nephroblastoma

Cited by 68 publications

References 38 publications

Growth Potential of Orbital Cavernous Hemangioma Suggested by Vascular Endothelial Growth Factor and its Receptor Flk-1

Growth Potential of Orbital Cavernous Hemangioma Suggested by Vascular Endothelial Growth Factor and its Receptor Flk-1

Immunohistochemical expression of p53, BCL-2, BAX and VEGFR1 proteins in nephroblastomas

Clinical Development of VEGF Signaling Pathway Inhibitors in Childhood Solid Tumors

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